{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:34:07Z","timestamp":1788950047267,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Optimal selection for perioperative therapy in urothelial carcinoma (UC) remains uncertain. We evaluated the efficacy of neoadjuvant and\/or adjuvant chemotherapy (NAC\/AC) for patients with bladder cancer (BC) and upper tract UC (UTUC), examined the role of lymphovascular invasion (LVI), and considered the implications for adjuvant nivolumab. Methods: We retrospectively analyzed consecutive patients who underwent radical cystectomy or radical nephroureterectomy at a single center (July 1998\u2013April 2021; observation to 31 March 2025). After exclusions, 252 BC and 153 UTUC patients were included. Endpoints were cancer-specific survival, progression-free survival (PFS; BC), non-urinary-tract recurrence-free survival (NUTRFS; UTUC), and overall survival (OS). Survival was estimated by Kaplan\u2013Meier analysis and compared by log-rank tests. Results: For BC, AC did not improve the PFS or OS in the overall pT \u2265 2 population, whereas node-positive (pN+) disease derived significant benefits in both endpoints among NAC-na\u00efve patients (PFS and OS, p = 0.002 and p = 0.008). For UTUC, AC conferred no advantage in NUTRFS or OS for the overall pT \u2265 2 population. However, NUTRFS benefits emerged in the pN+ subset (p = 0.049), although the OS was not improved. Among NAC-treated BC, the outcomes were poorest for \u2265ypT3 and ypN+, whereas ypT \u2264 2 fared better. LVI was associated with adverse outcomes and was borderline higher in pN+ versus pT \u2265 2\/pN\u2212 for BC (p = 0.056) and significantly higher for UTUC (p = 0.012). Conclusions: In this retrospective, single-center cohort, our exploratory analyses suggest that perioperative benefit is largely node-dependent, supporting prioritizing systemic therapy for pN+ disease and cautioning against routine AC for pT2\/ypT2 without nodal involvement. After NAC, adjuvant therapy appeared most justified for \u2265ypT3\/ypN+. Prospective biomarker-integrated validation is warranted and, given the small and underpowered subgroups and the potential for selection and immortal time biases, these observations should be interpreted as hypothesis-generating rather than causal.<\/jats:p>","DOI":"10.3390\/cancers17243986","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T13:32:37Z","timestamp":1765805557000},"page":"3986","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Perioperative Chemotherapy in Bladder and Upper Tract Urothelial Carcinoma: Outcomes by Nodal Status and Lymphovascular Invasion"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9159-493X","authenticated-orcid":false,"given":"Nobuki","family":"Furubayashi","sequence":"first","affiliation":[{"name":"Department of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka 811-1395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiro","family":"Tsujita","sequence":"additional","affiliation":[{"name":"Department of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka 811-1395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azusa","family":"Takayama","sequence":"additional","affiliation":[{"name":"Department of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka 811-1395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Shiraishi","sequence":"additional","affiliation":[{"name":"Department of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka 811-1395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motonobu","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka 811-1395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahito","family":"Negishi","sequence":"additional","affiliation":[{"name":"Department of Urology, National Hospital Organization Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka 811-1395, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.eururo.2025.02.019","article-title":"European Association of Urology Guidelines on Muscle-Invasive and Metastatic Bladder Cancer: Summary of the 2025 Guidelines","volume":"87","author":"Bruins","year":"2025","journal-title":"Eur. 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